A quantitative accounting of drug tranport, distribution, and loss in the precorneal portion of the eye, from an applied dose, has not been fully reported from any ophthalmic drugs and yet this information is essential to the development of proper dosing regimens, construction and evaluation of new drug delivery systems and further insight into drug toxicity considerations. Earlier work in this laboratory has estabished the influence of tear turnover and instilled fluid drainage on precorneal drug concentration, and, the influence of tear protein concentration and drug-protein binding on drug activity. In addition, we have investigated enzymatic degradation of drugs in the tears and studied corneal transport of drugs. The present proposal is designed to expand on this earlier work to give a concise quantitative picture of where a drug goes when placed in the eye, how much gets there together with the attendent rate and equilibrium constants. These objectives will be achieved, using pilocarpine nitrate, and, time permitting, fluoromethalone as representative drugs, by studying drainage and tear turnover loss of these drugs, corneal, conjunctival, and scleral absorption, as well as protein binding and enzymatic degradation in tears. The influence of these drugs on solution drainage and tear turnover will be studied using the technetium adsorbed colloid dilution technique that was developed in this laboratory. Eye tissue absorption studies will be conducted by both perfusion and non-perfusion techniques. The extent of drug binding to the proteins of tears will be studied using equilibrium dialysis techniques on whole tears as well as binding studies to albumin, lysozyme and globulin. Enzymatic degradation for these particular drugs will be verified by incubating the drugs with tears, aqueous humor and various ocular tissues. Data generated in these individual studies will be analyzed and then fit to a kinetic scheme, with the aid of a computer, to give a relatively complete picture of drug movement in the eye.